CLINICAL MYTHS AND EVIDENCE-BASED MEDICINE
Use of Flexible Bronchoscopy in the Diagnosis of Infectious
Etiologies: A Literature Review
Farnaz Houshmand, MD, Stella Ogake, MD, Mark R. Bowling, MD, FCCP,
and Craig Brown, MD
Abstract: Flexible bronchoscopy is a common tool utilized to assist
physicians in the diagnosis of suspected infectious disease of the
pulmonary system. This manuscript reviews the utility of broncho-
scopy for the management of infectious conditions.
Key Words: bronchoscopy, BAL, transbronchial biopsy, infectious
disease, pneumonia, AIDS, immunosuppressed
(Clin Pulm Med 2016;23:53–56)
S ince the invention of flexible bronchoscopy, its role in
obtaining specimens needed for the diagnosis of specific
pathogens in respiratory infections has been well appreciated,
as reflected by the literature dating back to the early 1970s.
Much of the robust body of data from case reports and early
studies in the subsequent 2 decades identified opportunistic
pathogens such as fungal and Nocardia infections successfully
in post-transplant patients as well as Pneumocystis jirovecii in
patients with acquired immunodeficiency syndrome (AIDS).
Cytomegalovirus (CMV) pneumonitis was also of interest in
earlier studies. However, we continue to be challenged in
determining when to pursue specimen sampling by broncho-
scopy [ie, bonchioalveolar lavage (BAL) or transbronchial
biopsy (TBBX)] as opposed to less invasive measures.
We reviewed the literature pertaining to nonventilated
patients with pulmonary infiltrates that are suspected to be
infectious. The reviewed data included both immunocompetent
and immunocompromised individuals. Immunocompromised
patients are further categorized as those with AIDS, those with
hematological malignancies [including status-post bone mar-
row transplant (BMT)], those on immunosuppressant drugs,
and neutropenic patients.
IMMUNOCOMPETENT PATIENTS
There has been very little focus on this subcategory. The
Infectious Diseases Society of America offers moderate rec-
ommendation for diagnostic respiratory specimens in severe
community-acquired pneumonias and an attempt to collect
lower respiratory specimens in health care–associated pneu-
monia, while acknowledging a lack of relevant studies. The
From the Department of Internal Medicine, Division of Pulmonary Critical
Care and Sleep Medicine, Brody School of Medicine, East Carolina
University, Greenville, NC.
Disclosure: M.R.B. is a paid consultant for Medtronic. The remaining
authors declare that they have no conflicts of interest.
Address correspondence to: Mark R. Bowling, MD, FCCP, Department of
internal medicine, Division of Pulmonary Critical Care and Sleep
Medicine, Brody School of Medicine, East Carolina University, 500
Moye Blvd., Greenville, NC 27858. E-mail: bowling@ecu.edu.
Copyright r 2016 Wolters Kluwer Health, Inc. All rights reserved.
ISSN: 1068-0640/16/2301-0053
DOI: 10.1097/CPM.0000000000000139
Clinical Pulmonary Medicine  Volume 23, Number 1, January 2016
Copyright r 2016 Wolters Kluwer Health, Inc. All rights reserved.
collection of specimens, nonetheless, should not delay empiric
treatment.1
In contrast, the issue of nonresolving pneumonias despite
antibiotic therapy has been a recurring interest. In a retro-
spective study, Feinsilver et al5 found fiberoptic bronchoscopy
to be instrumental in making the diagnosis in 12 of 14 (86%)
patients with a specific etiologic diagnosis in a population of
35 patients with nonresolving pneumonia.2 The study found
the procedure particularly beneficial in younger nonsmoking
patients who were symptomatic for 4 to 6 weeks and presented
with multilobar findings.
Arancibia et al3 showed a 57% diagnostic success rate
with TBBX in patients diagnosed with Community acquired
Pneumonia who failed initial antibiotic therapy. Of interest, a
Brazilian study by Joos et al4 assessed patients in intensive
care units who did not improve on antibiotics for respiratory
infections by performing BAL. The researchers found an
impressive positivity rate of 72% despite concurrent anti-
microbial treatment, suggesting that pathogen identification
can be feasible even after the initiation of therapy.5
IMMUNOCOMPROMISED PATIENTS
Since the discovery of the human immunodeficiency
virus (HIV) and associated AIDS, much research has focused
on the diagnostic approach to opportunistic infections. There
are very little data focusing on other common causes of res-
piratory infections as seen in immunocompetent patients.
A Spanish group studied 200 patients with non-HIV immuno-
suppression and reported a wide range of pathogens as causes of
pulmonary infiltrates.6 Commonly seen bacterial and viral
infections comprised more than half of the causes, whereas P.
jirovecii and Mycobacterium tuberculosis represented <5%.
Fungal infections also had a prominent presence. The study
found an improvement in the diagnosis by BAL from 31% to
43%, but did not show any change in the mortality.6
Second, a substantial patient population, commonly
referred to as non-AIDS immunocompromised, has been
studied. This group includes, but is not limited to, those who
have undergone BMT or have hematological malignancies,
and those who are on high-dose chemotherapy or cortico-
steroids. Despite the many new immunosuppressive medi-
cations used in recent years, we were not able to find a study
that addressed such a patient population.
In 2001, Tamm and colleagues studied the use of diag-
nostic bronchoscopy regarding pulmonary CMV infection in
580 patients including various immunocompromised groups as
well as immunocompetent patients. The immunocompromised
group consisted of HIV/AIDS, autoimmune disease, high-dose
chemotherapy treatment, renal transplant, and stem-cell
transplant. They reported similar rates of infection among all
immunocompromised groups, except those on high-dose che-
motherapy.7 They reported the immunostaining assay of the
www.clinpulm.com | 53
Houshmand et al
BAL specimen to be 100% and 57% diagnostic for CMV
pneumonitis and CMV disease, respectively. Diagnostic rates
exceeding 80% using BAL have been reported by others,8,9
which points out no added benefit of adding TBBX in such a
setting.
In contrast, Stover et al10 have shown that in non-HIV
immunocompromised patients, a combination of BAL and
TBBX improves diagnostic rate for lung infiltrate from 66%
and 68%, respectively, to 83% when combined. Similar results
have been shown by others, noting the added specific diag-
nostic advantage when TBBX is added to BAL, for HIV
patients as well as some oncology populations.9,11 Although
CMV was one of the pathogens diagnosed in the latter group, it
comprised a small portion. The difference in infectious causes
included in these studies may explain the finding of the added
benefit with TBBX, as opposed to none, in CMV pneumonitis.
A retrospective study by Cazzadori et al,12 which
included both immunocompromised and immunocompetent
patients, showed a higher diagnostic success rate with TBBX
as opposed to BAL for fungal infection and tuberculosis.
Another retrospective study showed an 83% success rate with
tuberculosis patients, especially in those who were unable to
produce sputum or had negative sputum despite a high clinical
suspicion.13
The AIDS Group
Swiss researchers compared occurrence rates of various
pulmonary infections among 1066 HIV patients between 2
sequential 6-year long periods: 1992 to 1998 against 1998 to
2003.4 They found bacterial and P. jirovecii infections to be
the leading pathogens among such patients. Furthermore, with
advancement of antiretroviral therapy, there was a clinically
significant change in the rate of bacterial and M. tuberculosis
infections.4
Appreciating the pathology involved with certain patho-
gens is essential in the choice of the appropriate technique
when obtaining specimens by bronchoscopy. For instance,
P. jirovecii is mostly in the alveolar space8; hence, upper-
airway sampling or transtracheal biopsy would not be benefi-
cial. Rather, BAL or TBBX, which would obtain the alveolar
tissue, gives the highest yield. The addition of TBBX to BAL
increased the diagnostic positivity from 74% to 95%.14 Similar
trends of improved results have been shown for the species
Cryptococcus and Aspergillus to be as high as 93%,15 but not
all studies show the added benefit of TBBX when testing for
P. jirovecii.8,11,16 One concern is the baseline-increased risk
of spontaneous pneumothorax in HIV patients, which is
increased when TBBX is performed. Baughman8 found quanti-
tative BAL to be representative of the burden of the disease. The
best results were with BAL obtained from areas with the highest
infiltrate density or the upper lobes. Similarly, Weldon-Linne
et al11 also found that the risk of adding TBBX is often not
needed for such patients undergoing BAL.
In contrast, M. tuberculosis can have a higher interstitial
presence than in the alveolar space, rendering a lower positive
yield on BAL,14 but a considerably improved yield when
combined with brushing and TBBX, such that up to 83% of the
actual infections can be diagnosed in those unable to produce
sputum or in those who have negative sputum cultures.4,13,17
Nontuberculous mycobacteria can be detected inter-
mittently in the sputum,14 posing a challenge to appropriate
diagnosis. In addition, their presence does not necessarily
mean infection, but can rather be colonization or con-
tamination of the sputum specimen. Hence, if separate sputum
samples cannot be collected, bronchial washes or lavage can be
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Clinical Pulmonary Medicine  Volume 23, Number 1, January 2016
attempted. The American Thoracic Society maintains that
TBBX can also be utilized to study histopathological or
microbiological cultures.18
Neutropenia
A small study compromising 58 patients with neutropenia
did not show any benefit of TBBX in terms of outcomes.19 It is
suggested that this is because these patients are empirically
started on a variety of antibiotics and sometimes antifungals at
the time of hospitalization.
Bone Marrow Transplant/Hematological
Malignancies
Respiratory complications are common in patients after
BMT. These complications account for significant morbidity
and mortality in this subsection of immunosuppressed patients.
It is therefore imperative to have accurate early diagnostic tests
that will lead to successful treatments to improve outcomes in
these patients.
Milburn and colleagues evaluated the role of BAL in the
evaluation of interstitial pneumonitis in recipients of BMT.20
Of 40 consecutive episodes of suspected pneumonitis in 30
patients, a positive diagnosis was made with bronchoscopy and
BAL in 32 lavage samples, giving a diagnostic yield of 80%.
CMV was the most common infectious etiology identified.20
Other infections isolated included Aspergillus fumigatus,
P. jirovecii, Pseudomonas aeruginosa, and Staphylococcus
aureus. Twenty years later, Huaringa and colleagues con-
ducted a retrospective study in 1999 of 89 BMT patients who
underwent bronchoscopy and BAL. This study revealed a
diagnostic yield of 47% with BAL.21 The most common
diagnosis made by BAL was an infectious etiology of pneu-
monia, which was 66% of all BAL. The 2 studies differed in
that a large portion of patients underwent a second and even a
third BAL when the first attempt was not diagnostic.21 This can
potentially contribute to the difference in the diagnostic yield
between the 2 studies.20,21
Shannon et al22 studied the utility of fiberoptic broncho-
scopy with BAL in the evaluation of new pulmonary infiltrates,
particularly as it relates to the optimal timing of the procedure.
They retrospectively evaluated 501 consecutive adults who
were BMT recipients and underwent 598 BALs to determine
whether diagnostic yields and patient outcomes differed on the
basis of early as against late referral for bronchoscopy. They
found that the overall yield for BAL was 55% for clinically
significant pathogens. The yield was 2.5-fold higher among
bronchoscopies performed early (within the first 4 d of pre-
sentation) compared with those performed later. The yield was
the highest (75%) if the bronchoscopy was performed within
24 hours of presentation. The authors reported that these
findings correlate with the significantly higher mortality of the
pulmonary etiology in those with a later diagnosis.22
Dunagan and colleagues conducted a retrospective study
to evaluate the impact of bronchoscopy and BAL on ther-
apeutic decisions and outcomes in BMT patients. They con-
cluded that bronchoscopy and BAL are diagnostically useful in
the evaluation of BMT patients with pulmonary complications
and often influence therapy, although no impact on survival
was demonstrated clearly.23
There have not been several studies to evaluate the role of
TBBX in the evaluation of pulmonary infiltrates in BMT
patients. However, other studies conducted on heterogeneous
groups of immunosuppressed patients suggest that TBBX
increases the diagnostic yield and may be more useful in
identifying interstitial diseases rather than infections. When
Clinical Pulmonary Medicine  Volume 23, Number 1, January 2016 Use of Flexible Bronchoscopy

higher risk of complications such as pneumothorax must be

TABLE 1. Description of the Optimal Bronchoscopic Approach to kept in mind when treating AIDS patients, or those with an
Various Infectious Conditions
increased risk of hemorrhage after TBBX. In addition, we
Patient Pathogen of suggest an early diagnostic attempt by BAL (with or without
Characteristics Concern Technique Comments TBBX) in post-BMT patients. The decision to add TBBX
Nonresolving BAL In younger, should be considered when noninfectious causes or, the
community nonsmoking interstitial pathology (infectious or noninfectious), are of
acquired patients who concern, emphasizing the similarities in clinical presentations
Pneumonia presented with or radiographic findings, which cannot be diagnosed without
multilobar appropriate choice of testing.
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history of
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Houshmand et al Clinical Pulmonary Medicine  Volume 23, Number 1, January 2016

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